U Raap1, N Deneka, M Bruder, A Kapp, B Wedi. 1. Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany. raap.ulrike@mh-hannover.de
Abstract
BACKGROUND: Recent studies suggest that neurotrophins have a pivotal role in neuroimmune interactions. Indeed, in contrast to nonatopic subjects (NA), neurotrophins have been shown to be increased in atopic diseases such as allergic rhinitis (AR) and atopic dermatitis (AD). AIM: The aim of the study was to assess the functional role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and -4 and the expression of pan-neurotrophin receptor (p75(NTR)) and tyrosine kinase (trk)A, -B and -C on peripheral blood eosinophils in AR, AD and NA. METHODS: Peripheral blood eosinophils of patients with AR, AD and NA were purified by CD16 negative selection (purity>98%). Neurotrophin receptor expression was analysed by FACS analysis. Apoptosis test (FACS analysis) and chemotactic index (modified Boyden chamber assay) were assessed after stimulation with BDNF, NT-3/-4 and NGF. RESULTS: The expression of trkA-C and p75(NTR) was significantly higher in AD>AR>NA (P<0.05-0.001). Apoptosis was significantly inhibited by BDNF, NGF, NT-3 in AD (P<0.05-0.001), by NT-3/-4 and NGF in AR (P<0.05-0.01) and by NT-3 (P<0.05-0.01) in NA eosinophils. Chemotaxis was significantly induced by BDNF and NT-3/4 (P<0.01-0.001) in AD peripheral blood eosinophils. CONCLUSION: Neurotrophin receptor expression and neurotrophin functional activity was greatest in AD>AR>NA. AD eosinophils are pre-activated and may therefore better respond to neurotrophins. With this study, we provide new pathophysiologic insights into atopic diseases with a functional role of neurotrophins in peripheral blood eosinophils in AD and AR.
BACKGROUND: Recent studies suggest that neurotrophins have a pivotal role in neuroimmune interactions. Indeed, in contrast to nonatopic subjects (NA), neurotrophins have been shown to be increased in atopic diseases such as allergic rhinitis (AR) and atopic dermatitis (AD). AIM: The aim of the study was to assess the functional role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and -4 and the expression of pan-neurotrophin receptor (p75(NTR)) and tyrosine kinase (trk)A, -B and -C on peripheral blood eosinophils in AR, AD and NA. METHODS: Peripheral blood eosinophils of patients with AR, AD and NA were purified by CD16 negative selection (purity>98%). Neurotrophin receptor expression was analysed by FACS analysis. Apoptosis test (FACS analysis) and chemotactic index (modified Boyden chamber assay) were assessed after stimulation with BDNF, NT-3/-4 and NGF. RESULTS: The expression of trkA-C and p75(NTR) was significantly higher in AD>AR>NA (P<0.05-0.001). Apoptosis was significantly inhibited by BDNF, NGF, NT-3 in AD (P<0.05-0.001), by NT-3/-4 and NGF in AR (P<0.05-0.01) and by NT-3 (P<0.05-0.01) in NA eosinophils. Chemotaxis was significantly induced by BDNF and NT-3/4 (P<0.01-0.001) in AD peripheral blood eosinophils. CONCLUSION:Neurotrophin receptor expression and neurotrophin functional activity was greatest in AD>AR>NA. AD eosinophils are pre-activated and may therefore better respond to neurotrophins. With this study, we provide new pathophysiologic insights into atopic diseases with a functional role of neurotrophins in peripheral blood eosinophils in AD and AR.